CHMP4B
charged multivesicular body protein 4B, the group of Charged multivesicular body proteins|ESCRT-III
Basic information
Region (hg38): 20:33811348-33854366
Previous symbols: [ "C20orf178" ]
Links
Phenotypes
GenCC
Source:
- cataract 31 multiple types (Strong), mode of inheritance: AD
- early-onset posterior polar cataract (Supportive), mode of inheritance: AD
- early-onset posterior subcapsular cataract (Supportive), mode of inheritance: AD
- cataract 31 multiple types (Strong), mode of inheritance: AD
- cataract 31 multiple types (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cataract 31, multiple types | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Ophthalmologic | 10682967; 10909854; 17701905 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cataract_31_multiple_types (13 variants)
- not_provided (10 variants)
- not_specified (6 variants)
- CHMP4B-related_disorder (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHMP4B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000176812.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | |||||
| missense | 11 | 14 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 1 | 12 | 2 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CHMP4B | protein_coding | protein_coding | ENST00000217402 | 5 | 43063 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.958 | 0.0422 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.38 | 53 | 129 | 0.411 | 0.00000734 | 1473 |
| Missense in Polyphen | 12 | 45.522 | 0.26361 | 517 | ||
| Synonymous | -0.0583 | 55 | 54.5 | 1.01 | 0.00000361 | 408 |
| Loss of Function | 2.92 | 0 | 9.90 | 0.00 | 4.30e-7 | 137 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (PubMed:12860994, PubMed:18209100). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:26040712}.;
- Disease
- DISEASE: Cataract 31, multiple types (CTRCT31) [MIM:605387]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT31 includes posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular cataracts. {ECO:0000269|PubMed:17701905}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Endocytosis - Homo sapiens (human);Necroptosis - Homo sapiens (human);Disease;Vesicle-mediated transport;Membrane Trafficking;Budding and maturation of HIV virion;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;Endosomal Sorting Complex Required For Transport (ESCRT);Infectious disease
(Consensus)
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- loftool
- rvis_EVS
- -0.08
- rvis_percentile_EVS
- 47.79
Haploinsufficiency Scores
- pHI
- 0.643
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.571
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Chmp4b
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- mitotic cytokinesis;posttranslational protein targeting to endoplasmic reticulum membrane;autophagy;nucleus organization;vacuolar transport;mitotic metaphase plate congression;exit from mitosis;regulation of centrosome duplication;endosomal transport;macroautophagy;viral life cycle;nuclear envelope reassembly;multivesicular body assembly;maintenance of lens transparency;viral budding via host ESCRT complex;viral budding;regulation of viral process;protein homooligomerization;negative regulation of cell death;midbody abscission;membrane fission;ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway;negative regulation of neuron death;regulation of mitotic spindle assembly;positive regulation of viral release from host cell;negative regulation of autophagosome assembly
- Cellular component
- ESCRT III complex;nucleus;nuclear envelope;cytoplasm;endosome;cytosol;cytoplasmic side of plasma membrane;membrane coat;midbody;late endosome membrane;vesicle;extracellular exosome
- Molecular function
- protein binding;identical protein binding;protein homodimerization activity;cadherin binding